DNA variations impact immune host response through the perturbations they cause to transcriptional and biological networks, providing a molecular phenotype* that is an intermediate to the clinical phenotype. By integrating expression quantitative trait loci (eQTLs), gene expression, and clinical data, we are now able to infer transcriptional networks capable of representing causal relationships among genes and traits in the network. This provides the opportunity to identify multiple genetic perturbations that alter the states of molecular networks and that in turn move systems into disease states. Specifically, by dissecting immunogenetic traits, we are able to elucidate key drivers of immune host response beyond what could be achieved by traditional genetic association studies alone. The Systems Immunogenetics core (Core D) will provide critical statistical genetics and computational biology expertise to the U19 investigators across all projects by guiding experimental design with appropriate biostatistical oversight, providing state-of-the-art systems genetics analysis and modeling approaches and ensuring that the vast amounts of data generated are rapidly integrated to identify key genetic regulators of immune phenotype and response to SARS, Influenza and West Nile Viruses.